1 / 29

Controversies in Adjuvant Therapy for Pancreatic Cancer

Controversies in Adjuvant Therapy for Pancreatic Cancer. Parag Sanghvi M.D. Tasha McDonald M.D. Department of Radiation Medicine OHSU. Median Survival of Patients With Pancreatic Cancer. Localized/ Resectable 15-19 months 10% Locally Advanced 6-10 months 30%

ancelin
Télécharger la présentation

Controversies in Adjuvant Therapy for Pancreatic Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Controversies in Adjuvant Therapy for Pancreatic Cancer Parag Sanghvi M.D. Tasha McDonald M.D. Department of Radiation Medicine OHSU

  2. Median Survival of Patients With Pancreatic Cancer • Localized/ Resectable 15-19 months 10% • Locally Advanced 6-10 months 30% • Metastatic/ Advanced 3-6 months 60%

  3. Adjuvant Therapy • No clear consensus on adjuvant therapy for pancreatic cancer • Difference in philosophy between Europe & North America • Europeans have moved to adjuvant chemotherapy alone

  4. Adjuvant ChemoRT

  5. GITSG (1985) • 43 pts randomized into two groups • XRT/bolus 5-FU  5FU X 2 years vs. Observation • Split course radiation – total dose 40 Gy • Median survival – 20 vs. 11 months • 2 y OS – 43% vs. 18%

  6. EORTC (1999) • Phase III randomized trial • Adjuvant chemoRT vs. observation • Split course RT (40 Gy) with concurrent 5 FU vs. Observation • Median survival 24.5 months vs. 19.0 months (p = 0.21) • 2 y OS 41% vs. 51% (p = 0.21)

  7. EORTC (1999)

  8. EORTC (1999) • Criticism is that this study included patients with ampullary tumors • Improved benefit of adjuvant therapy seen in patients with pancreatic head tumors • 2 y OS 34 % vs. 26% (p = 0.099) • MS 17.1 months vs. 12.6 months

  9. ESPAC 1 (2001) • Randomized trial with 2 X 2 factorial design • Patients randomized to • Chemoradiation • Chemoradiation followed by Chemotherapy • Chemotherapy alone • Observation • Radiation was split course RT (total dose 40Gy; 2 week course) • Chemotherapy was 5FU + Leucovorin

  10. ESPAC 1 (2001)

  11. ESPAC 1 (2001)ChemoRT vs. No ChemoRT • MS 15.9 months vs. 17.9 months • 2 y OS 29% vs. 41% (p = 0.05)

  12. ESPAC 1 (2001)Chemotherapy vs. No Chemotherapy • MS 20.1 vs. 15.5 months (p = 0.009) • 2 y OS 40% vs. 30%

  13. ESPAC 1 (2001)Criticisms • Split course RT; No central review of RT • Doses ranged from 40-60 Gy; treatment not uniform or not delivered in 30% patients • Significant protocol violations in all arms; cross-over allowed

  14. Newer Trials • CONKO -001 (2007) • Adjuvant chemotherapy vs. observation • RTOG 9704 (ASCO 2006)

  15. CONKO-001 (2007)Oettle et al. (JAMA) • Randomized Phase III European trial; 368 patients • T1-4 N0-1 M0 pancreatic cancer • R0 or R1 resection • Chemotherapy • Started 10-42 d after surgery • 6 cycles of Gemcitabine q 4 weeks • Each cycle – 3 weekly infusions 1000mg/m2

  16. CONKO-001 (2007) • Results • Median DFS 13.4 months vs. 6.9 months (p < 0.001) • R0 13.1 months vs. 7.3 months • R1 15.8 months vs. 5.5 months • OS MS 22.1 vs. 20.2 months (p = 0.06) • Overall, 83% of all patients had relapses

  17. CONKO-001 (2007)

  18. RTOG 9704 (ASCO 2006) • 538 patients enrolled; 442 eligible & analyzable • T1-T4 N0-1 M0 • 381 pancreatic head lesions • Patients randomized to pre and post chemoRT 5FU vs. pre and post chemoRT gemcitabine

  19. RTOG 9704Treatment Paradigm

  20. RTOG 9704 Results • No statistically significant difference in OS between the two arms when all patients analyzed • However, patients with pancreatic head lesions showed significantly improved survival in the Gemcitabine arm • MS 36.9 months vs. 20.6 months • 3 y OS 32% vs. 21%

  21. RTOG 9704Results

  22. RTOG 9704Results • No real gains in survival seen in this 1st RCT with modern doses / treatment technique compared to historical RCT with split course lower dose RT

  23. Adjuvant Radiation Therapy in Surgically Resected Pancreatic Cancer: SEER Database • 1973 - 2003 • 2636 patients with resectable pancreatic cancer • 1123 received adjuvant RT • 1513 did not receive any adjuvant therapy • Median F/U 19 months

  24. Adjuvant Radiation Therapy in Surgically Resected Pancreatic Cancer: SEER Database • Median Survival • Adjuvant RT vs. No RT – 18 months vs. 11 months (p <0.001) • Cox regression showed HR 0.57 (0.52,0.63; p<0.01) • Independent statistically significant factors linked to decreased survival • African Americans • Moderate & Poorly diff. adenoCA • Age <60 • Stage

  25. Mayo Clinic Experience • Retrospective review of 472 consecutively treated patients with R0 resection • T1-3 N0-1 M0 • 1975-2005 • If adjuvant chemoRT given • Median dose 50.4 Gy • 98% received concurrent 5FU based chemotherapy

  26. Mayo Clinic ExperienceResults

  27. Mayo Clinic ExperienceResults

  28. Future Trials – ESPAC 3

  29. Conclusions • Obvious controversies in management of pancreatic cancer • All randomized trials have significant flaws • What we need (but will not get) is a well designed RCT • Our design: 3 arms, no cross-over • Observation • Adjuvant chemotherapy (gemcitabine) • Adjuvant chemoRT (5-FU with RT to 50.4 Gy followed by gemcitabine)

More Related